On the bromination of the dihydroazulene/vinylheptafulvene photo-/thermoswitch

Article abstract of DOI:10.3762/bjoc.8.108

Background: The dihydroazulene (DHA)/vinylheptafulvene (VHF) system (with two cyano groups at C1) functions as a photo-/thermoswitch. Direct ionic bromination of DHA has previously furnished a regioselective route to a 7,8-dibromide, which by elimination was converted to a 7-bromo-substituted DHA. This compound has served as a central building block for functionalization of the DHA by palladium-catalyzed cross-coupling reactions. The current work explores another bromination protocol for achieving the isomeric 3-bromo-DHA and also explores the outcome of additional bromination of this compound as well as of the known 7-bromo-DHA.

Full text of DOI:10.3762/bjoc.8.108

On the bromination of the dihydroazulene/
vinylheptafulvene photo-/thermoswitch
Virginia Mazzanti1,2, Martina Cacciarini1,3, Søren L. Broman1,
Christian R. Parker1, Magnus Schau-Magnussen1, Andrew D. Bond4
and Mogens B. Nielsen*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 958–966.
1Department of Chemistry, University of Copenhagen,
Universitetsparken 5, DK-2100 Copenhagen Ø, Denmark,
2Sino-Danish Center for Education and Research (SDC), Niels
Jensens Vej 2, DK-8000 Aarhus C, Denmark, 3Department of
Chemistry, University of Florence, via della Lastruccia 3-13, I-50019,
Sesto F.no, Italy and 4Department of Physics, Chemistry and
Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230
Odense M, Denmark
doi:10.3762/bjoc.8.108
Received: 28 February 2012
Accepted: 23 May 2012
Published: 27 June 2012
This article is part of the Thematic Series "Molecular switches and cages".
Guest Editor: D. Trauner
Email:
Mogens B. Nielsen* - mbn@kiku.dk
© 2012 Mazzanti et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
azulene; bromination; dihydroazulene; molecular switches;
photoswitch; vinylheptafulvene
Abstract
Background: The dihydroazulene (DHA)/vinylheptafulvene (VHF) system (with two cyano groups at C1) functions as a photo-/
thermoswitch. Direct ionic bromination of DHA has previously furnished a regioselective route to a 7,8-dibromide, which by elimi-
nation was converted to a 7-bromo-substituted DHA. This compound has served as a central building block for functionalization of
the DHA by palladium-catalyzed cross-coupling reactions. The current work explores another bromination protocol for achieving
the isomeric 3-bromo-DHA and also explores the outcome of additional bromination of this compound as well as of the known
7-bromo-DHA.
Results: Radical bromination on two different VHFs by using N-bromosuccinimide/benzoyl peroxide and light, followed by a ring-
closure reaction generated the corresponding 3-bromo-DHAs, as confirmed in one case by X-ray crystallography. According to a
1H NMR spectroscopic study, the ring closure of the brominated VHF seemed to occur readily under the reaction conditions. A
subsequent bromination–elimination protocol provided a 3,7-dibromo-DHA. In contrast, treating the known 7-bromo-DHA with
bromine generated a very labile species that was converted to a new 3,7-dibromoazulene, i.e., the fully unsaturated species.
Azulenes were also found to form from brominated compounds when left standing for a long time in the solid state. Kinetics
measurements reveal that the 3-bromo substituent enhances the rate of the thermal conversion of the VHF to DHA, which is oppo-
site to the effect exerted by a bromo substituent in the seven-membered ring.
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Conclusion: Two general procedures for functionalizing the DHA core with a bromo substituent (at positions 3 and 7, respectively)
are now available with the DHA as starting material.
Introduction
1,8a-Dihydroazulene-1,1-dicarbonitrile (DHA, 1) is a yellow
photochromic compound, which undergoes a light-induced
10-electron retro-electrocyclization to a red-colored vinylhepta-
fulvene (VHF) (Scheme 1) [1-3]. The VHF compound is
formed as the s-cis conformer, which, however, is in equilib-
rium with the more stable s-trans conformer. The s-cis VHF
Scheme 2: Bromination–elimination protocol for functionalization of
DHA [3,5-8]. HMDS = hexamethyldisilazide.
undergoes a thermally induced cyclization to regenerate the
original DHA. The significant structural difference between the
DHA and VHF forms, as reflected in their different colors and
hence electronic properties, renders the system interesting as a particularly convenient for making VHF on a preparative scale,
light-controlled molecular switch in, for example, molecular which is more tedious when employing a light source. Along
electronics. Indeed, light-induced conductance switching was this line, we became interested in investigating the possibility of
recently observed for a DHA derivative situated in a single- brominating the VHF 2. It was previously shown by Kuroda
molecule junction [4]. For the further exploration of the and Asao [11] that the related VHF 5 underwent bromination by
DHA/VHF switch in this field, ongoing synthetic efforts are N-bromosuccinimide (NBS) to form the product 6 (Scheme 3),
required for the incorporation of functional groups onto the but any thermal conversion of this VHF to a DHA was not
system, especially in a regioselective manner.
described. Here we describe NBS bromination of VHF 2 and
isolation of the corresponding 3-bromo-DHA. In addition, the
outcome of further bromination of this compound as well as of
the 7-bromo-DHA 4 is presented.
Scheme 1: Dihydroazulene (DHA)/vinylheptafulvene (VHF) photo-/
thermoswitch.
Scheme 3: Bromination of VHF [11]. NBS = N-bromosuccinimide.
We have recently developed an efficient protocol for functional-
Results and Discussion
izing the DHA/VHF 1/2 (R = Ph) at position 7 (for numbering,
see Figure 1) by a bromination–elimination protocol of 1, as Synthesis
shown in Scheme 2 [3,5-8]. Elimination of HBr from the inter- DHA 1 was first opened to VHF 2 by aluminum chloride fol-
mediate 3 provided the bromo-functionalized DHA 4 that was lowed by quenching with water according to a previously
employed for further cross-coupling reactions. The advantage of described procedure (Scheme 4) [10]. The resulting VHF 2 was
this method is that the “parent DHA” 1 can be prepared on a then treated with NBS and benzoyl peroxide in benzene and the
large scale in a few steps [9] and it is hence a convenient mixture was subjected to irradiation from a 500 W halogen
building block for further functionalization. Moreover, we have lamp source, presumably generating the intermediate, but short-
found that the treatment of DHA by aluminum chloride fol- lived (see below), species 7. No structural evidence for 7 was
lowed by water provided another means of inducing ring- obtained, but after standard work-up, the ring-closed 3-bromo-
opening of DHA to form VHF (Scheme 1) [10]. This method is DHA product 8 was isolated in an overall yield of 46%,
suggesting that 7 is indeed formed as an intermediate. The
structure of 8 was elucidated by a 1H,1H COSY NMR spec-
trum (Figure 2) and ultimately confirmed by X-ray crystallo-
graphic analysis (Figure 3a). Interestingly, when following the
bromination by 1H NMR spectroscopy, signals from the VHF 2
seem absent within 5 min, while instead signals from the DHA
Figure 1: Numbering of azulene.
8 quickly emerge (Figure 4). There are, however, some signals
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Beilstein J. Org. Chem. 2012, 8, 958–966.
Scheme 4: Radical and ionic brominations of VHF.
around 6.5 and 7.3 ppm (Figure 4c and Figure 4d) from uniden- mination, the 3-bromo-DHA 10 was formed in almost quantita-
tified intermediates, which decrease in intensity after irradi- tive yield (estimated yield of 95%) instead of the benzylic bro-
ation for longer time. No characteristic signals from the mide product. This compound was, however, difficult to purify
suggested bromo-VHF intermediate 7 were observed, thus it without significant loss of material. When subjecting VHF 2 to
must undergo rapid ring closure to the DHA 8 under the reac- bromination by Br2 (Scheme 4), under the same conditions used
tion conditions although the mixture is subjected to light.
to regioselectively brominate the corresponding DHA 1, many
products (unidentified) were formed according to NMR spec-
Interestingly, when the known tolyl derivative 9 [12] (Figure 5) troscopy. Thus, ionic bromination is not a useful method for the
was subjected to the ring opening followed by NBS bro- functionalization of the VHF. Gratifyingly, we managed to
Figure 2: 1H,1H COSY NMR spectrum of DHA 8 (CDCl3, 500 MHz). For assignments of DHA signals, see numbering in Figure 1.
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Beilstein J. Org. Chem. 2012, 8, 958–966.
Figure 3: Molecular structures (with displacements ellipsoids at 50% probability for non-H atoms) of (a) DHA 8 (CCDC 868717; crystals were grown
from butanone/heptane); (b) VHF 2 (CCDC 866016; crystals were grown from benzene/cyclohexane; benzene cocrystallized with the VHF but has
been omitted for clarity); (c) azulene 14 (CCDC 868718; crystals were grown from dichloromethane/heptane); (d) azulene 15 (CCDC 868719; crystals
were grown from dichloromethane/heptane).
Figure 4: 1H NMR spectra (C6D6, 300 MHz) of (a) DHA 1; (b) VHF 2; (c–e) VHF 2 after treatment with 2 molar equiv of NBS in the presence of
benzoyl peroxide and irradiation for 5, 15, and 35 min, respectively.
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Beilstein J. Org. Chem. 2012, 8, 958–966.
Scheme 5: Synthesis of 3,7-dibromo-DHA.
Figure 5: Compound 9 was selectively brominated to furnish the pro-
duct 10.
grow crystals suitable for X-ray diffraction studies of the VHF 2
(generated by the AlCl3-induced ring opening of DHA 1 fol-
lowed by a liquid–liquid extraction) by layering cyclohexane
upon a solution of the VHF in benzene and allowing this mix-
ture to crystallize at 5 °C (lower temperatures and nonpolar
solvents reduce the rate of the undesired thermal back reaction
[9]). The crystal structure of VHF 2 is shown in Figure 3b.
Scheme 6: Synthesis of a 3,7-dibromoazulene.
The two bromo positions of 14 showed very different reactivity.
With the objective to generate DHA building blocks with more Thus, subjecting 14 to a Sonogashira coupling with triisopro-
than one bromo functionality for further reactions, we subjected pylsilylacetylene by using the Pd(PPh3)2Cl2/CuI catalyst system
the 3-bromo-DHA 8 to the ionic bromination–elimination only gave the monocoupled product 15 (Scheme 7), confirmed
protocol, which, via the intermediate 11, provided the 3,7- by X-ray crystal structure analysis (Figure 3d). Moreover, a
dibromo-substituted DHA 12 (Scheme 5). In an alternative Suzuki cross-coupling reaction with boronic acid 16 gave the
strategy (Scheme 6), we started out with the 7-bromo-DHA 4. product 17, albeit in rather low yield (Scheme 7). The substitu-
Treatment with bromine at −78 °C generated in this case, tion was confirmed by NOESY 1D experiments (see Supporting
however, a very labile intermediate, tentatively assigned to the Information File 1).
structure 13, which underwent ready conversion, without the
addition of base, to the azulene 14 together with a complex mix- Finally, we observed that upon storage at room temperature, the
ture of other nonisolated products. This product is not dibromide 3 as well as the known tetrabromide 18 [5] slowly
surprising, inasmuch as we have previously found that a solu- turned into a mixture of azulenes, which we isolated and identi-
tion of the related dibromide 3 over time underwent conversion fied as 19–22 shown in Scheme 8. While, 19 (X-ray crystal
to a mixture of 1-bromo-3-cyano-2-phenylazulene and 1-cyano- structure is given in [6]), 20 [5], and 21 [5,14,15] are already
2-phenylazulene [5]. The conversion of 13 into azulenes was, known, the dibromoazulene 22 is new.
however, so fast that we could not perform the controlled elimi-
nation of HBr by LiHMDS to generate the corresponding 7-bro- UV–vis absorption and switching studies
mo-DHA as we could from 3. The structure of the azulene 14 The UV–vis absorption spectrum of the 3-bromo-DHA 8 in
was confirmed by X-ray crystallographic analysis (Figure 3c). cyclohexane is shown in Figure 6. The compound exhibits an
Functionalized azulenes are themselves interesting in materials absorption maximum at 337 nm, which is blue-shifted by 17 nm
chemistry for their optical and redox properties [13].
relative to that of DHA 1 [9]. By irradiation at 337 nm, the
Scheme 7: Regioselective Sonogashira and Suzuki couplings. RuPhos = 2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl.
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Beilstein J. Org. Chem. 2012, 8, 958–966.
Scheme 8: Slow conversions to azulenes in the solid state.
DHA was gradually converted to the VHF 7 (Figure 6) exhibit- tron withdrawal, hence stabilizing a zwitterionic VHF tran-
ing a characteristic absorption maximum at 453 nm (blue- sition state, as previously suggested [9]. In accordance hereto,
shifted by 7 nm relative to that of VHF 2 [9]). Upon heating of we have previously found that moving the bromo substituent to
the VHF at 50 °C, a gradual conversion to the DHA was the seven-membered ring has the opposite effect; thus, the VHF
observed. Although both the light-induced DHA-to-VHF derived from 7-bromo-DHA 4 underwent ring closure consider-
conversion and the thermally induced VHF-to-DHA conver- ably slower than VHF 2 [7]. We are, however, not able to
sion were found to occur with isosbestic points in the absorp- explain the remarkably fast formation of 8 from 7 under the
tion spectra, we found that the conversion was not fully revers- bromination conditions described above, but it may be the result
ible. First, the VHF could not be fully converted to DHA of the slight Lewis acidity under the reaction conditions.
(Figure 6, broken curve), and, second, when a second cycle was
performed, the final VHF absorption was at a lower intensity Conclusion
than after the first conversion. Nevertheless, the decay of the In conclusion, we have developed a method for functionalizing
VHF absorption could be fitted to an exponential decay (see the DHA/VHF photo-/thermoswitch with a bromo substituent at
Supporting Information File 1).
position 3 in the DHA core (product 8). The synthesis explores
the ready conversion of DHA 1 to VHF 2 on a preparative scale
by using aluminum chloride followed by NBS bromination.
This bromination was found to occur selectively in the pres-
ence of a tolyl group (product 10). The method contrasts the
earlier bromination (Br2)–elimination protocol on DHA for
incorporating selectively a bromo substituent at position 7 in the
DHA core without proceeding via the VHF as an intermediate.
Subjecting the 3-bromo-DHA 8 to this bromination–elimina-
tion protocol furnished the 3,7-dibromo-DHA 12. In contrast,
subjecting the 7-bromo-DHA 4 to an additional bromination
with Br2 generated a very labile compound that was readily
converted to the fully unsaturated 3,7-dibromo-substituted azul-
ene 14 together with other unidentified products. The insta-
bility of intermediate bromide addition products was also
reflected by solid-state conversions of di- and tetrabromides to a
variety of azulenes. The influence on the thermal VHF-to-DHA
Figure 6: Absorption spectra of DHA 8 and VHF 7 in cyclohexane. The
broken curve shows the absorption spectrum after one light–heat cycle
(DHA → VHF → DHA).
From this fit, we obtained rough estimates of the rate constant conversion exerted by a bromo substituent at position 3 (DHA
and half-life of k = 5.1 × 10−4 s−1 and t1/2 = 27 min at 50 °C. numbering) is opposite to that of one at position 7; the former
For comparison, the values for conversion of VHF 2 to DHA 1 substitution enhances the ring closure while the latter retards it.
in cyclohexane are 8.3 × 10−5 s−1 and t1/2 = 139 min at 50 °C The new bromo-substituted compounds will be interesting for
(found from Arrhenius plot, [9]). Thus, the influence of the bro- future scaffolding in the quest for advanced photo- and ther-
mo substituent in 7 is to enhance significantly the rate of the moswitches. We note, however, that initial attempts at using the
thermal ring closure, which is explained by its inductive elec- 3-bromo-substituted DHA for Sonogashira or Suzuki couplings
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Beilstein J. Org. Chem. 2012, 8, 958–966.
(as previously accomplished for the 7-bromo-substituted DHA) 111.9, 48.8, 47.4 ppm; FABMS m/z: [M]+ 334; Analysis calcd
have so far been unsuccessful. It seems that the 3-bromo func- for C18H11BrN2: C, 64.50; H, 3.31; N, 8.36; found: C, 63.90;
tionality is not very reactive, which is reflected as well by the H, 3.42; N, 7.86.
regioselective Sonogashira and Suzuki reactions on the 3,7-
dibromoazulene 14 reported in this work.
3-Bromo-2-(4-methylphenyl)-1,8a-dihydroazulene-1,1-dicar-
bonitrile (10): To a stirred solution of 2-(4-methylphenyl)-1,8a-
dihydroazulene-1,1-dicarbonitrile (9) (250 mg, 0.97 mmol) in
CH2Cl2 (30 mL) at rt was added AlCl3 (760 mg, 5.74 mmol).
Experimental
General Methods
NMR spectra were measured on 300 or 500 MHz instruments. Stirring was continued for a further 10 min and then the mix-
All chemical shift values in the 1H and 13C NMR spectra are ture was quenched with water (50 mL). The organic layer was
referenced to the solvent (δH = 7.26 ppm, δC = 77.16 ppm). separated, dried over Na2SO4, filtered, and concentrated under
Thin-layer chromatography (TLC) was carried out on commer- reduced pressure. The residue was then dissolved in benzene
cially available precoated plates (silica 60) with fluorescence (50 mL), and NBS (1.60 g, 9.50 mmol) was added. The solu-
indicator; color change of the spot from yellow (DHA) to red tion was stirred under an Ar atmosphere for 10 min and then
(VHF) upon irradiation by UV light indicated the presence of a benzoyl peroxide (3 mg, 0.01 mmol) was added. The solution
DHA. For column chromatographic purification of DHAs, the was irradiated with a 500 W halogen lamp for 2 h. The mixture
column was covered by aluminium foil to exclude light; the was filtered and washed with water. The organic layer was
isolated fractions were also kept in the dark. All melting points washed with saturated aqueous NaHCO3 solution (3 × 150 mL),
are uncorrected. All spectroscopic measurements (including dried over anhydrous Na2SO4, and filtered. The solvent was
photolysis of DHA to VHF and kinetics studies on the thermal removed under reduced pressure affording 10 with minor impu-
conversion of VHF to DHA) were performed in a cuvette of rities (321 mg, estimated yield of 95%). An analytically pure
1 cm path length. Photoswitching experiments were performed sample (yellow solid) could be obtained by dry column vacuum
by using a 150 W xenon arc lamp equipped with a monochro- chromatography (SiO2, Et2O/heptane 3:2). Rf 0.79 (30% ethyl
mator. Elemental analyses were performed at the Department of acetate/heptane); mp 115 °C; 1H NMR (500 MHz, CDCl3) δ
Chemistry, University of Copenhagen.
7.62 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 6.67 (dd, J =
11.3, 6.4 Hz, 1H), 6.58–6.49 (m, 2H), 6.34 (ddd, J = 10.1, 6.1,
3-Bromo-2-phenyl-1,8a-dihydroazulene-1,1-dicarbonitrile 2.1 Hz, 1H), 5.76 (dd, J = 10.1, 4.0 Hz, 1H), 3.79–3.72 (m, 1H),
(8): To a stirred solution of DHA 1 (300 mg, 1.17 mmol) in 2.43 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ 140.8, 136.6,
CH2Cl2 (40 mL) at rt was added AlCl3 (800 mg, 6.01 mmol). 136.0, 131.6, 130.3, 129.7, 128.6, 128.1, 127.8, 126.2, 121.8,
Stirring was continued for further 20 min and then the mixture 119.6, 114.4, 112.0, 48.8, 47.3, 21.5 ppm; EIMS m/z: [M]+ 348;
was quenched with water (60 mL). The organic layer was sep- Analysis calcd for C19H13BrN2: C, 65.35; H, 3.75; N, 8.02;
arated, dried over anhydrous Na2SO4, filtered, and concen- found: C, 65.50; H, 3.54; N, 7.94.
trated under reduced pressure. The resulting red compound was
then dissolved in benzene (40 mL) and NBS (700 mg, 3,7-Dibromo-2-phenyl-1,8a-dihydroazulene-1,1-dicarboni-
3.93 mmol) was added. The solution was stirred under an Ar trile (12): 3-Br-DHA 8 (85 mg, 0.25 mmol) was dissolved in
atmosphere for 10 min and then benzoyl peroxide (13 mg, CH2Cl2 (5 mL) at −78 °C under a N2 atmosphere and the mix-
0.05 mmol) was added. The solution was irradiated with a ture was excluded from light. Then a solution of Br2 in CH2Cl2
500 W halogen lamp kept at a distance of ca. 1 m from the reac- (0.78 M, 327 µL) was slowly added over 2 min. The mixture
tion mixture. After 4 h, the mixture was filtered and washed was stirred for 30 min at −78 °C and then concentrated in vacuo
with water. The organic layer was washed with saturated to yield the crude product 11 as a yellow-brown solid (126 mg,
aqueous NaHCO3 solution (3 × 100 mL), dried over anhydrous 0.25 mmol). This compound was used without purification for
Na2SO4, and filtered. The solvent was removed under reduced the next step. It was dissolved in dry THF (5 mL) and cooled to
pressure and the crude residue was purified by dry column −78 °C. Then LiHMDS (0.3 mL, 0.3 mmol, 1 M in toluene) was
vacuum chromatography (SiO2, 60% Et2O/heptane) affording 8 added dropwise, and the solution was stirred for 2 h, while the
(180 mg, 46%) as a yellow solid. Rf 0.73 (30% heptane/ temperature was slowly raised to rt. The reaction mixture was
EtOAc); mp 126 °C; 1H NMR (500 MHz, CDCl3) δ 7.63 (m, diluted with Et2O (20 mL) and then washed with saturated
2H), 7.44 (m, 3H), 6.61 (dd, J = 11.3, 6.4 Hz, 1H), 6.50 (d, J = aqueous NH4Cl (2 × 50 mL). The organic phase was dried over
6.1 Hz, 1H), 6.49–6.46 (m, 1H), 6.28 (ddd, J = 10.1, 6.1, anhydrous Na2SO4 and filtered. The solvent was removed under
2.1 Hz, 1H), 5.70 (dd, J = 10.1, 4.0 Hz, 1H), 3.70 (m, 1H) ppm; reduced pressure and the crude residue was purified by dry
13C NMR (125 MHz, CDCl3) δ 136.5, 135.8, 131.8, 130.8, column vacuum chromatography (SiO2, 50% Et2O/heptane)
130.4, 130.3, 129.0, 128.8, 128.10, 126.9, 122.1, 119.6, 114.3, affording 12 (68 mg, 65%) as a pale green solid. Mp 118 °C;
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Beilstein J. Org. Chem. 2012, 8, 958–966.
1H NMR (300 MHz, CDCl3) δ 7.78–7.64 (m, 2H), 7.61–7.46 RuPhos (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-
(m, 3H), 6.63 (d, J = 3.6 Hz, 2H), 6.52 (dt, J = 3.6, 1.7 Hz, 1H), biphenyl) (24 mg, 0.051 mmol). The mixture was vigorously
6.08 (d, J = 4.5 Hz, 1H), 3.80 (dd, J = 4.5, 1.7 Hz, 1H) ppm; stirred and heated at 100 °C for 4 d. Purification by flash
13C NMR (125 MHz, CDCl3) δ 138.3, 137.9, 133.8, 131.3, column chromatography (SiO2, CH2Cl2) afforded 17 (15 mg,
130.7, 130.3, 129.1, 128.7, 126.4, 121.2, 120.4, 120.2, 113.7, 26%) as a blue solid. Mp 169–171 °C; 1H NMR (500 MHz,
111.5, 49.0, 46.9 ppm; Analysis calcd for C18H10Br2N2: C, CDCl3) δ 8.81 (d, J = 1.7 Hz, 1H), 8.56 (dd, J = 10.0, 0.9 Hz,
52.21; H, 2.43; N, 6.76; found: C, 52.58; H, 2.41; N, 6.69. 1H), 8.00 (ddd, J = 10.2, 1.7, 0.9 Hz, 1H), 7.86–7.83 (m, 2H),
7.64 (t, J = 10.1 Hz, 1H), 7.60–7.55 (m, 2H), 7.53–7.47 (m,
3,7-Dibromo-2-phenylazulene-1-carbonitrile (14): To a solu- 1H), 7.06–6.88 (m, 3H), 3.85 (s, 3H), 3.80 (s, 3H) ppm;
tion of 4 excluded from light (154 mg, 0.46 mmol) (prepared as 13C NMR (125 MHz, CDCl3) δ 154.1, 151.0, 150.6, 142.5,
previously described [12]) in CH2Cl2 (4 mL) at −78 °C under a 142.4, 139.5, 139.4, 139.3, 137.2, 133.3, 132.9, 130.3, 129.5,
N2 atmosphere was slowly added a 0.78 M solution of Br2 128.8, 127.7, 117.2, 117.1, 114.6, 113.0, 104.2, 96.8, 56.5,
(0.59 mL, 0.46 mmol) in CH2Cl2. After being stirred for 10 min 56.1 ppm; HRMS–ESI (m/z): [M + H]+ calcd for
at −78 °C, the reaction mixture was concentrated in vacuo. C25H19BrNO2, 444.0594; found, 444.0617.
Purification by flash column chromatography (SiO2, 50%
CH2Cl2/heptane) afforded 14 (71 mg, 40%) as a green solid. Solid-state conversion of dibromide 3 into azulenes
Mp 220–223 °C; 1H NMR (500 MHz, CDCl3) δ 8.89 (d, J = (19–21)
2.1 Hz, 1H), 8.52 (d, J = 9.9 Hz, 1H), 8.17 (dd, J = 10.4, The dibromide 3 (416 mg, 1.00 mmol) was stored in the dark at
1.8 Hz, 1H), 7.84 (m, 2H), 7.64–7.49 (m, 3H), 7.38 (t, J = rt in a closed vessel (50 mL) for 30 d. The resulting black solid
10.4 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ 152.5, was dissolved in CH2Cl2 and purification by dry column
143.3, 141.7, 139.5, 139.4, 137.2, 132.7, 130.3, 130.0, 128.9, vacuum chromatography (SiO2, 12.6 cm2, 0–100% toluene/
127.4, 124.4, 116.3, 105.4, 96.1 ppm; GC–MS (m/z): [M]+ heptanes, 12.5% steps, then 0–35% CH2Cl2 in toluene, 7%
386.9; HRMS–ESI (m/z): [M + H]+ calcd for C17H10Br2N, steps, 40 mL fractions) gave 19 (119.4 mg, 57%) and an insepa-
385.9175; found, 385.9196.
rable mixture (ca. 4:1) of 20 and 21 (55.8 mg, 24%) (known
compounds: [5,14,15]).
3-Bromo-2-phenyl-7-(triisopropylsilylethynyl)azulene-1-
carbonitrile (15): To a mixture of the azulene 14 (18 mg, 2-Phenylazulene-1,3-dicarbonitrile (19): 1H NMR (500 MHz,
0.047 mmol), Pd(PPh3)2Cl2 (4 mg) and CuI (2 mg) in argon- CDCl3) δ 8.80 (d, J = 9.7 Hz, 2H), 8.08 (t, J = 9.7 Hz, 1H), 8.05
degassed THF (4 mL) under an Ar atmosphere were added (d, J = 7.4 Hz, 2H), 7.87 (t, J = 9.7 Hz, 2H), 7.62 (t, J = 7.4 Hz,
iPr2NH (40 μL, 0.283 mmol) and triisopropylsilylacetylene 2H), 7.58–7.55 (m, 1 H) ppm; 13C NMR (125 MHz, CDCl3) δ
(30 μL, 0.134 mmol). After being stirred for 24 h at rt, add- 155.6, 145.4, 141.7, 138.1, 131.8, 131.7, 130.9, 129.7, 129.6,
itional triisopropylsilylacetylene (50 μL, 0.223 mmol) was 116.1, 97.0 ppm; for X-ray data, see [6].
added, and the mixture was stirred again for 24 h at rt. Concen-
tration of the reaction mixture in vacuo and purification of the Solid-state conversion of tetrabromide 18 into
residue by flash column chromatography (50% CH2Cl2/ azulenes 19, 20, and 22
heptane) afforded 15 (17.5 mg, 77%) as a green solid. Mp The tetrabromide 18 (576 mg, 1.00 mmol) was stored in the
181–183 °C; 1H NMR (500 MHz, CDCl3) δ 8.72 (d, J = 1.5 Hz, dark at rt in a closed vessel (50 mL) for 30 d. The resulting
1H), 8.51 (dd, J = 9.9, 0.7 Hz, 1H), 8.03 (ddd, J = 10.4, 1.5, black solid was dissolved in CHCl3 and purification by flash
1.0 Hz, 1H), 7.86–7.80 (m, 2H), 7.60–7.56 (m, 2H), 7.54–7.51 column chromatography (SiO2, toluene) gave 19 (78.9 mg,
(m, 1H), 7.51 (t, J = 10.2 Hz, 1H), 1.22–1.16 (m, 21H) ppm; 38%) as a pink solid, 20 (50.8 mg, 17%) as a violet solid, and
13C NMR (125 MHz, CDCl3) δ 151.9, 143.7, 142.1, 139.4, 22 (97.7 mg, 20%) as a green solid. TLC (toluene); Rf
139.2, 138.0, 132.9, 130.3, 129.8, 128.8, 127.4, 124.1, 116.5, 0.06–0.09 (19), 0.25–0.30 (20), 0.43–0.47 (22).
108.9, 106.0, 97.6, 95.1, 18.9, 11.5 ppm; HRMS–ESI (m/z):
[M + H]+ calcd for C28H31BrNSi, 488.1404; found, 488.1398. 3,6-Dibromo-2-phenylazulene-1-carbonitrile (22): 1H NMR
(300 MHz, CDCl3) δ 8.32 (d, J = 8.2 Hz, 1H), 8.28 (d, J =
3-Bromo-7-(2’,5’-dimethoxyphenyl)-2-phenylazulene-1- 8.6 Hz, 1H), 7.94 (dd, J = 5.2 Hz, J = 1.9 Hz, 1H), 7.90 (dd, J =
carbonitrile (17): To a solution of the azulene 14 (50 mg, 4.6 Hz, J = 1.9 Hz, 1H), 7.81–7.85 (m, 2H), 7.49–7.61
0.129 mmol) and 2,5-dimethoxyphenylboronic acid (16) (m, 3H) ppm; 13C NMR (75 MHz, CDCl3) δ 151.3, 142.1,
(47 mg, 0.259 mmol) under an Ar atmosphere in an argon- 138.6, 137.9, 136.2, 134.4, 132.8, 132.2, 131.7, 130.2, 129.8,
degassed toluene/water 9:1 mixture were added K3PO4 128.9, 116.2, 106.6, 98.5 ppm; Analysis calcd for C17H9Br2N:
(110 mg, 0.517 mmol), Pd(OAc)2 (6 mg, 0.0026 mmol) and C, 52.75; H, 2.34; N, 3.62; found: C, 52.97; H, 2.03; N, 3.55.
965

Beilstein J. Org. Chem. 2012, 8, 958–966.
14.Nozoe, T.; Takase, K.; Fukuda, S. Bull. Chem. Soc. Jpn. 1971, 44,
2210–2213. doi:10.1246/bcsj.44.2210
Supporting Information
15.Gierisch, S.; Daub, J. Chem. Ber. 1989, 122, 69–75.
doi:10.1002/cber.19891220112
Supporting Information File 1
1D and 2D NMR spectra of all new compounds. Table of
bond lengths for VHF 2 (X-ray crystallographic data).
Exponential fit of the decay over time of the VHF 7
absorbance at the longest-wavelength absorption
maximum.
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Acknowledgements
Financial support from The Sino-Danish Center for Education
and Research (SDC) and The Danish Council for Independent
Research/Natural Sciences (#10-082088) is acknowledged. Mr.
Christian G. Tortzen is gratefully acknowledged with regard to
NMR characterizations.
The license is subject to the Beilstein Journal of Organic
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